<i>Aspergillus fumigatus</i>MADS-Box Transcription Factor<i>rlmA</i>Is Required for Regulation of the Cell Wall Integrity and Virulence

G3: Genes, Genomes, Genetics - Tập 6 Số 9 - Trang 2983-3002 - 2016
Marina Campos Rocha1, João Henrique Tadini Marilhano Fabri1, Krissia Franco de Godoy1, Patrícia Alves de Castro2, Juliana Issa Hori3, Anderson Ferreira da Cunha1, Mark Arentshorst4, Arthur F. J. Ram4, Cees A. M. J. J. van den Hondel4, Gustavo H. Goldman2, Iran Malavazi1
1Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, 13565 São Carlos, São Paulo, Brazil
2Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brazil
3Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049 Ribeirão Preto, São Paulo, Brazil
4Molecular Microbiology and Biotechnology, Institute of Biology, Leiden University, 2333 Leiden, The Netherlands

Tóm tắt

AbstractThe Cell Wall Integrity (CWI) pathway is the primary signaling cascade that controls the de novo synthesis of the fungal cell wall, and in Saccharomyces cerevisiae this event is highly dependent on the RLM1 transcription factor. Here, we investigated the function of RlmA in the fungal pathogen Aspergillus fumigatus. We show that the ΔrlmA strain exhibits an altered cell wall organization in addition to defects related to vegetative growth and tolerance to cell wall-perturbing agents. A genetic analysis indicated that rlmA is positioned downstream of the pkcA and mpkA genes in the CWI pathway. As a consequence, rlmA loss-of-function leads to the altered expression of genes encoding cell wall-related proteins. RlmA positively regulates the phosphorylation of MpkA and is induced at both protein and transcriptional levels during cell wall stress. The rlmA was also involved in tolerance to oxidative damage and transcriptional regulation of genes related to oxidative stress adaptation. Moreover, the ΔrlmA strain had attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Our results suggest that RlmA functions as a transcription factor in the A. fumigatus CWI pathway, acting downstream of PkcA-MpkA signaling and contributing to the virulence of this fungus.

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G3: Genes, Genomes, Genetics

Tập 6 Số 9

2983-3002

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